Light-Switched Anesthetics Allow Researchers to turn Pain Nerves On and Off

A new study published in the journal Nature Methods, shows that a novel local anesthetic developed by a group of researchers at UC Berkeley, University of Münich, and the Université de Boardeaux, can be switched on and off using different wavelengths of light, allowing a much finer control of which nerves are blocked.

Local anesthetics, which work by blocking the flow of sodium ions across neuronal cell membranes, have been in use for well over a century. Cocaine was the first drug used in this fashion, but it was superseded by a variety of synthetic alternatives.

The new molecule, called quaternary ammonium-azobenzene-quaternary ammonium (QAQ), resembles lidocaine, but it comes in two forms, cis and trans. The trans form can be converted to the cis form by a 380 nm light. In the dark, QAQ slowly reverts back to the trans form. This can be achieved rapidly by using a 500 nm light.

Once inside a cell, the trans form of QAQ blocks many different ion channels while the cis version remains inactive.

However, QAQ is a fairly large molecule which usually doesn’t cross cell membranes. This could allow QAQ to be a very selective local anesthetic. Pain-sensing neurons (nocieptive) contain many ion channels, which are activated by stimuli. One of the main channels is called TRPV1, which is activated by capsaicin, heat and other inflammatory mediators.

When activated for a prolonged period, TRPV1 receptors dilate, and the pores become large enough for bigger molecules, such as QAQ, to pass through the cell membranes. This means that the anesthetic could actively target the pain receptors that sense pain, where it can be turned on and off by different wavelengths of light.